GWAS of Schizophrenia
Schizophrenia Schizophrenia is a mental disorder mostly characterized by abnormal social behavior and the failure to recognize reality. Typical symptoms are comprised of false beliefs, unclear thought processes, hallucinations, decreased social interaction and expression of emotion, and inactivity. Genetics, early environment, and both psychological and social process play large roles in the development of schizophrenia, however it is unclear as to whether it is a solitary disorder or a plethora of separate syndromes. Dopamine suppressing antipsychotic medication is the most widely-used form of treatment, while counseling, job training, and social rehabilitation are important as well. Affecting about 0.3-0.7% of people, schizophrenia mainly affects the ability to think and causes chronic behavioral and emotional problems that may lead to conditions such as major depression and anxiety disorders. This can all result in serious social issues, leaving those affected unemployed, poor, and homeless. Due to an increased rate of physical health problems and a higher suicide rate among those affected, the average life expectancy of someone with schizophrenia is ten to twenty five years less than the average life expectancy (1). Schizophrenia and Genetics Although the path of the disorder is still not fully understood, genome-wide association study of schizophrenia indicates that genetics play a large, if not dominant role in the development of the condition. To date, there are over 100 loci associated with schizophrenia that have been identified through the most recent genome-wide association study (2). Scientists looked at over 80,000 genetic samples from schizophrenia patients and healthy volunteers, replicating SNPs in multiple genomic regions. They soon found 108 specific locations in the human genome associated with schizophrenia. 83 of those loci had not been linked to the disorder before this study. It has been found that up to 10,200 SNPs may contribute to risk for schizophrenia and collectively account for at least 32% of the variability among the disorder (3). A study posted this year finds that of the 108 loci identified, 75% include protein-coding genes. It made notable associations relevant to major hypotheses of the cause of schizophrenia including genes DRD2 (involved in encoding dopamine receptors), GRM3, GRIN2A, SEE, GRIA1 (involved in glutamatergic neurotransmission and synaptic plasticity, and CACNA1C, CACNB2, CACNA1I (involved in encoding voltage-gated calcium channel subunits). In short, genes encoding calcium channels as well as proteins involved in glutamatergic neurotransmission and synaptic plasticity are shown to contribute to schizophrenia when in variation, affecting neurotransmission including genes that are active in pathways essential for learning and memory. Additionally, these scientists found a smaller number of genes correlating with schizophrenia that are active within the immune system (2). SNPs Some of the growing number of SNPs found to be linked to schizophrenia are: *rs10790212 *rs11743803 in the ACSL6 gene *rs175174 in the ZDHHC8 gene; possibly not related to schizophrenia *in the TPH1 gene **rs1800532 **rs211105 **rs7933505 *in the SYN2 gene **rs310762 **rs795009 *in the DISC1 gene **rs3738401 **rs751229 *rs6675281 in the DISC2 gene *in or near the COMT gene **rs4680 **rs165599 *rs4938445 in the FXYD6 gene *rs4950928 *rs497768 *in the ERBB4 gene **rs839523 **rs7598440 **rs707284 *rs947267 in the DAOA gene *rs27388 in the MEGF10 gene *rs2270641 in the SLC18A1 gene *rs17101921 on ch 10q25-26 *rs833497 in the DYM gene *In the SREBF1 and SREBF2 genes **rs11868035 **rs1057217 *In the dopamine D2 receptor DRD2 gene **rs1801028 **rs6277 *In the NXRN1 gene **rs2024513, in Han Chinese *rs4129148 near the CSF2RA gene *rs28694718 and rs28414810, part of a haplotype block in intron 8 of the CSF2RA gene *rs6422441, rs6603272, and rs17883192, all part of a haplotype block spanning introns 4, 5 and 6 of the IL3RA gene **rs1801028 **rs6277 **rs11225703, on chromosome 11 **rs2848745, on chromosome 18 **rs17651507, on chromosome 17 **rs2437896, on chromosome 2 **rs2499846, on chromosome 1 **rs4958803, on chromosome 5 **rs2053149, on chromosome 14 **rs7582658, on chromosome 2 **rs2119783, on chromosome 8 (4). References 1. Wikipedia. "Schizophrenia". 2014. 2. Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). "Biological insights from 108 schizophrenia-associated genetic loci". Nature. Vol 511. pp. 421-427. 3. Ripke S. et al (2013). "Genome-wide association analysis identifies 13 new risk loci for schizophrenia." National Genetics. Vol 45. pp. 1150-9. 4. SNPedia. "Schizophrenia". 2014.